Antioxidative roles of sesamin, a functional lignan in sesame seed, and it's effect on lipid- and alcohol-metabolism in the liver: A DNA microarray study
Antioxidative roles of sesamin, a functional lignan in sesame seed, and it's effect on lipid- and alcohol-metabolism in the liver: A DNA microarray study
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DOI：
10.1002/biof.552210139
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发表时间：
2004-01-01
期刊：
影响因子：
6
通讯作者：
Kiso, Y
中科院分区：
文献类型：
--
作者：
Kiso, Y
大鼠经口给予芝麻素，定期采集血液、胆汁和尿液。给药后24小时，在胆汁中检测到超过40%的芝麻素剂量为2-（3，4-亚甲二氧基苯基）-6-（3，4-二羟基苯基）-顺-二氧杂双环[3.3.0]辛烷和2-（3，4-二羟基苯基）-6-（3，4-二羟基苯基）-顺-二氧杂双环[3.3.0]辛烷的葡萄糖醛酸苷。对这些代谢产物的抗氧化活性进行了比较，儿茶酚代谢产物不仅对超氧阴离子自由基，而且对羟自由基都有较强的清除活性。提示芝麻素经门静脉途径吸收，经肝细胞药物代谢酶代谢为单或双邻苯二酚代谢产物。两种代谢产物在肝脏中均表现出抗氧化活性，最终与葡萄糖醛酸结合并在胆汁中排泄。芝麻素可归类为抗氧化剂前体。比较了给予芝麻素或溶剂的大鼠肝脏基因表达谱。芝麻素显著提高了β-氧化后期酶（包括三功能酶、酰基辅酶A氧化酶、双功能酶和3-酮脂酰辅酶A硫解酶）的基因表达水平。另一方面，编码脂肪酸合成酶的基因的转录减少。此外，在芝麻素大鼠中，醛脱氢酶的基因表达增加了约3倍，而醇脱氢酶、肝脏过氧化氢酶和CYP 2 E1没有变化。这些结果表明，芝麻素摄入调节肝脏脂质和酒精代谢酶的转录水平。
Sesamin was orally administered to rats, and blood, bile and urine were collected periodically. Over 40% of the dose of sesamin was detected in bile as glucuronides of 2-(3, 4-methylenedioxyphenyl)-6-(3, 4-dihydroxyphenyl)-cis-dioxabicyclo[3.3.0] octane and 2-(3, 4-dihydroxyphenyl)-6-(3, 4-dihydroxyphenyl)-cis-dioxabicyclo[3.3.0] octane by 24 hr after administration. Antioxidant activities of these metabolites were compared and catechol metabolites showed strong radical scavenging activities against not only superoxide anion radical but also hydroxyl radical. It was suggested that sesamin was absorbed by the route of portal vein and metabolized to mono- or di-catechol metabolite by drug metabolizing enzymes in the liver cells. Both metabolites exhibited antioxidant activity in the liver and were finally conjugated with glucuronic acid and to excrete in bile. Sesamin can be classified as a pro-antioxidant.The profiles of gene expression of the liver in rats given sesamin or vehicle were compared. The gene expression levels of the late stage enzymes of beta-oxidation including trifunctional enzyme, acyl-CoA oxidase, bifunctional enzyme and 3-ketoacyl-CoA thiolase were significantly increased by sesamin. On the other hand, the transcription of the genes encoding the enzymes for fatty acid synthesis was decreased. Moreover, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about 3-fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for lipids and alcohol.